Development of fullerene derivatives for new anti-cancer and and-virus drugs lead compounds
Project/Area Number |
17590092
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Drug development chemistry
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Research Institution | Kyoritsu University of Pharmacy |
Principal Investigator |
MASHINO Tadahiko Kyoritsu University of Pharmacy, Department of Pharmaceutical Sciences, Professor (90165697)
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Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Shigeo Kyoritsu University of Pharmacy, Department of Pharmaceutical Sciences, Associate Professor (00264078)
TAKAHASHI Kyoko Kyoritsu University of Pharmacy, Department of Pharmaceutical Sciences, Assistant Professor (90255381)
NISHIZAWA Thiho Kyoritsu University of Pharmacy, Department of Pharmaceutical Sciences, Post doctoral fellow (50448990)
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Project Period (FY) |
2005 – 2007
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Project Status |
Completed (Fiscal Year 2007)
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Budget Amount *help |
¥3,710,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥210,000)
Fiscal Year 2007: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2006: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
|
Keywords | Fullerene / anti-cancer drug / and HIV drug / anti-hepatitis C virus drug / HIV reverse transcriptase / hepatitis C virus RNA polymerase / apoptosis / がん細胞増殖抑制 / HIV逆転写酵素阻害 / C型肝炎ウィルス増殖抑制 / がん細胞増殖抑制効果 / 抗菌活性 |
Research Abstract |
1. Cancer cell proliferation inhibition mechanism of fullerene derivatives. It had already been reported that the pyrrolidinium type fullerene derivative (1) showed the cancer cell proliferation inhibition effect. We investigated the mechanism of inhibition using HL-60 cell line. Treatment of 1 induced the features of apoptosis and also induced the Caspase 3 and 9 activation and cytochromec release from mitochondria. But p53 induction was not observed. It is thought that the compound causes apoptosis without p53 induction is advantageous as the anti-cancer drug, because p53 is loss in cancer cells in many cases. 2. Design and synthesis of praline type fullerene derivatives with high HIV reverse transcriptase inhibition activity. Using the computer docking simulation, various fullerene derivatives were designed and synthesized based on the structure of derivative (2) that had three carboxylic acids in the pyrrole ring. Relationship between the inhibition activity and number and position of carboxylic acid acids in the pyrrole ring was investigated and more active derivative 3 was developed. The inhibition activity of 3 was 100 times or more high than Nevirapin, which is used as and HIV drug. 3. Anti-hepatitis C virus activity of fullerene derivatives Sulfonium type fullerene derivative (4) showed excellent hepatitis C virus RNA polymerase inhibition activity and hepatitis C virus growth inhibition activities. Cytotoxicity of 4 was low. 4 is a promising lead compound of the anti-hepatitis C virus medicine. In this three years project, we developed the novel promising lead compounds for anti-cancer, anti-HIV, and anti-HCV medicine.
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Report
(4 results)
Research Products
(82 results)
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[Journal Article] C_60 Nanowhisker Field-Effect-Transistor Application for Nana-Electronics2008
Author(s)
Ogawa, K., Aoki, N., Miyazawa, K., Nakamura, S., Mashino, T., Bird, J P, Ochiai Y*
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Journal Title
Jpn J Appl Phys 47(1)
Pages: 501-504
Description
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[Journal Article] Novel Metabolic Pathways of p-n-NonylphenoI Catalyzed by Cytochrome P450 and Estrogen Receptor Binding Activity of New Metabolites2007
Author(s)
Tezuka, Y., Takahashi, K., Suzuki, T., Kitamura, S., Ohta, S., Nakamura, S., Masluno, T*
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Journal Title
J Health Sci 53(5)
Pages: 552-561
Description
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[Journal Article] Synthesis of novel amino acid-type fullerenes and their inhibition activity of HN reverse transcriptase and HCV RNA polymerase2006
Author(s)
Nakamura, S., Ikegami, N., Harada, M., Shimotohno, K., Takahashi, K., Mashino, T*
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Journal Title
J Kyoritsu Univ Pharm 1
Pages: 77-84
Description
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[Journal Article] Structural characterization of room-temperature synthesized fullerene nanowhiskers2006
Author(s)
Miyazawa, K*., Minato, J., Mashino, T., Nakamura, S., Fujino, M., Suga, T
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[Presentation] Synthesis of sulfonium fullerene derivatives with anti HCV activity2008
Author(s)
Mod, Y., Shimotohno, K., Takahashi, K., Nakamura, S., Mashino, T
Organizer
128th Annual Meeting of the Pharmaceutical Society of Japan
Place of Presentation
Yokohama, Japan
Description
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[Presentation] HIV reverse transcriptase inhibition activity of 5-aryl praline-type fullerene derivatives2008
Author(s)
Akiho, Y., Takeuchi, Y., Takahashi, K., Nakamura, S., Mashino, T
Organizer
128th Annual Meeting of the Pharmaceutical Society of Japan
Place of Presentation
Yokohama, Japan
Description
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[Presentation] 抗HCV活性を有する新規フラーレン誘導体2007
Author(s)
中村 成夫, 笠原 優子, 深澤 征義, 森裕 美子, 高橋 恭子, 下遠野 久美子, 増野 匡彦
Organizer
第26回メディシナルケミストリーシンポジウム
Place of Presentation
相模原
Year and Date
2007-11-23
Description
「研究成果報告書概要(和文)」より
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[Presentation] Antioxidant Activity of Fullerene Derivative Lacking Prooxidant Activity2007
Author(s)
Nakamura, S., Satake, E., Hatanaka, M., Takahashi, K., Mashino, T
Organizer
211th Meeting of The Electrochemical Society
Place of Presentation
Chicago, USA
Description
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[Presentation] Generation of Reactive Oxygen Species by Antiproliferative Fullerene Derivative2007
Author(s)
Nishizawa, C., Hashimoto, N., Takahashi, K., Nakamura, S., Mashino, T
Organizer
211th Meeting of The Electrochemical Society
Place of Presentation
Chicago, USA
Description
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[Presentation] TEM and Raman Spectroscopy Analyses of Fullerene Nanowhiskers and Nanotubes2007
Author(s)
Miyazawa, K., Ringor C, Nakamura, K., Tachibana, M., Mashino, T., Nakamura, S
Organizer
Nanotech 2007
Place of Presentation
Santa Clara, USA
Description
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[Presentation] Synthesis, TEM and Raman spectroscopic analysis of Nano whisker from fullerene derivatives2007
Author(s)
Mashino, T., Nakamura, S., Saito, K., Kizuka, T., Miyazawa, K
Organizer
68th The Japan Society of Applied Physics, autumn meeting
Place of Presentation
Sapporo, Japan
Description
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[Presentation] Fullerene derivatives have antioxidant activity but no metal-dependent pro oxidant activity2007
Author(s)
Nakamura, S., Satake, E., Hatanaka, M., Takahashi, K., Matsubayashi, K., Mashino, T
Organizer
The 32th Fullerene-Nanotubes General Symposium
Place of Presentation
Nagoya, Japan
Description
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[Presentation] Antiproliferative cationic fullerene derivatives induce oxidative stress in HL-60 cell2007
Author(s)
Nishizawa, C., Hashimoto, N., Mori, Y., Takahashi, K., Nakamura, S., Mashino, T
Organizer
127th Annual Meeting of the Pharmaceutical Society of Japan
Place of Presentation
Toyama, Japan
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Design and synthesis of novel praline-type fullerene derivatives that have HIV reverse transcriptase inhibition activity2007
Author(s)
Akiho, Y., Yokoo, S., Takahashi, K., Nakamura, S., Mashino, T
Organizer
127th Annual Meeting of the Pharmaceutical Society of Japan
Place of Presentation
Toyama, Japan
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Apoptosis induction by the antiproliferative cationic fullerene derivative2007
Author(s)
Hashimoto, N., Nishizawa, C., Takahashi, K., Nakamura, S., Mashino, T
Organizer
127th Annual Meeting of the Pharmaceutical Society of Japan
Place of Presentation
Toyama, Japan
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Apoptosis induction and generation of reactive oxygen species by cationic fullerene derivative2007
Author(s)
Nishizawa, C., Hashimoto, N., Takahashi, K., Nakamura, S., Mashino, T
Organizer
29th Annual Meeting of the Society of Free Radical, Japan
Place of Presentation
Nagoya, Japan
Description
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[Presentation] Synthesis of diastereomers of sulfonium fullerene derivatives with anti HCV activity2007
Author(s)
Akiho, Y., Takeuchi, Y., Takahashi, K., Nakamura, S., Mashino, T
Organizer
51th Annual Meeting of the Pharmaceutical Society of Japan Kanto Branch
Place of Presentation
Tokyo, Japan
Description
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[Presentation] New proline-type fullerene derivatives that have HIV reverse transcriptase inhibition activity2007
Author(s)
Nakamura, S., Kasahara, Y., Fukasawa, M., Mod, Y., Takahashi, K., Shimotohno K, Mashino, T
Organizer
26th Medicinal Chemistry Symposium
Place of Presentation
Sagamihara, Japan
Description
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[Presentation] Human Immunodeficiency Virus-Reverse Transcriptase Inhibition and Hepatitis C Virus RNA-Dependent RNA Polymerase Inhibition Activities of Fullerene Derivatives2006
Author(s)
Mashino, T., Shimotohno, K., Ikegami, N., Takahashi, K., Nakamura, S., Mochizuki M
Organizer
209th Meeting of The Electrochemical Society
Place of Presentation
Denver, USA
Description
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[Presentation] Raman spectroscopic analyses of fullerene nanotubes and nanowhiskers2006
Author(s)
Miyazawa, K., Mashino, T., Nakamura, S., Tachibana, M., Nakamura, K., Suga, T
Organizer
Nanotube 06 : Seventh International Conference on the Science and Application of Nanotubes
Place of Presentation
Nagano, Japan
Description
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[Presentation] Effect and the mechanism of HIV reverse transcriptase inhibition by proline-type fullerene derivatives2006
Author(s)
Ikegami, N., Takahashi, K., Nakamura, S., Shimotohno, K., Mochizuki, M., Mashino, T
Organizer
126th Annual Meeting of the Pharmaceutical Society of Japan
Place of Presentation
Sendai, Japan
Description
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[Presentation] Ambient-temperature preparation of fullerene-nanowhisker and -nanotube, and its physical properties2006
Author(s)
Miyazawa, K., Minato, J., Kato, R., Anzaka, K., Kizuka, T., Mashino, T., Nakamura, S., Taxhibana, M., Suga, T
Organizer
Physical-sensor Symposium
Place of Presentation
Tokyo, Japan
Description
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[Presentation] Antioxidant and prooxidant activity off fullerene derivative2006
Author(s)
Satake, E., Takahashi, K., Nakamura, S., Mashino, T., Matsubayashi, K
Organizer
28th Annual Meeting of the Society of Free Radical, Japan
Place of Presentation
Tsu, Japan
Description
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[Presentation] Induction of reactive oxigen wpecies bt antiproliferative cationic fullerene derivatives in HL-60 cell2006
Author(s)
Nishizawa, C., Hashimoto, N., Takahashi, K., Nakamura, S., Mashino, T
Organizer
21th Annual Meeting of the Society of Free Radical, Japan Kanto Branch
Place of Presentation
Tokyo, Japan
Description
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[Presentation] フラーレン類の医療への応用2005
Author(s)
増野 匡彦、中村 成夫、宮澤 薫一
Organizer
ナノテクアセス研究会
Place of Presentation
東京
Year and Date
2005-04-13
Description
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[Presentation] Characterization of the Liquid-Phase Synthesized Fullrene Nanotube and Nanowhisker2005
Author(s)
Miyazawa, K., J., Minato J, T., Mashino, T., Yoshii, T., Kizuka, T., Kato, R., Tachibana, M., Suga, T
Organizer
The 13th JSME Materials and Processing Conference
Place of Presentation
Seattle, USA
Description
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[Presentation] Structural characterization of room-temperature synthesized fullerene nanowhiskers2005
Author(s)
Miyazawa, K., Minato, J., Mashino, T., Nakamura, S., Fujino, M., Suga, T
Organizer
2nd Poland-Japan Workshop on Material Science
Place of Presentation
Warsaw, Poland
Description
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[Presentation] Inhibition of HIV-reverse transcriptase by mono- or bis-substituted fullerene derivatives2005
Author(s)
Ikegami, N., Shimotohno, K., Nishikawa, D., Takahashi, K., Nakamura, S., Mochizuki M., Mashino, T
Organizer
International Chemical Congress of Pacific Basin Societies2005
Place of Presentation
Honolulu, USA
Description
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